Resting (Go) T-cells purified from the spleens of young (2-4 mo.) and old (24-27 mo.) C57BL/6 mice were used in studies to examine the effect of age on the trans-membrane signalling mechanism involving the phospholipase C induced hydrolysis of phosphatidyl- inositol 4,5 bisphosphate. Mitogenic doses of Concanavalin A (Con A) effectively induced the translocation of protein kinase C (PK-C) from cytosol to membrane in cells from young mice but in cells from old mice the level of PK-C translocated was reduced to approximate half of the level observed in the young. Total PK-C levels were the same in Go T-cells from young and old mice and phorbol 12 myristate 13 acetate (PMA) translocated equivalent levels of the enzyme irrespective of the age of the donor. Con A induced a greater change in intracellular calcium concentrations in the Go T-cells from the young mice as compared to the old both in the presence and absence of extracellular calcium. Also the detectable levels of inositol phosphates were reduced in the Con A stimulated Go T-cells from old mice. The level of these molecules, which are involved in regulating intracellular calcium concentration, were also reduced by approximately 50% of that detected in cells from young mice. PK-C levels and the capacity to translocate from cytosol to membrane were the same in T lymphocytes from young (less than 35 yrs) and old (greater than 70 yrs) human males in response to PMA. In response to PHA, T- cells from some but not all old subjects translocated low levels of PK-C. Studies are planned to extend the investigation using human T-cells to determine intracellular calcium levels and to correlate deficiencies in the transmembrane signalling mechanism with expression of functional IL-2 receptors and/or Il-2 production. Murine Go T-cells from